Most Super-fund sites are contaminated with metals mixtures and organic chemicals and a major concern for human exposure to Superfund sites is the possibility of disease, and in particular, cancer induction. This SBRP competing application has two major themes: 1) Carcinogenic metals have unique as well as multiple mechanisms in causing cancers and can synergize with other environmental carcinogens (i.e. PAHs, PCBs and UV) to induce cancers and developmental toxicities;and 2) Environmental mixtures also affect metal reactivity in sediments. Thus, the molecular mechanisms of Ni(ll), chromate and arsenite carcinogenesis will be examined in detail to add more depth to our knowledge of this important research. In particular, how these metals interact with other environmental agents such as UV, PAHs and PCBs and how these agents interact mechanistically with metals to cause cancer will be investigated. In addition, the unique molecular mechanisms by which metals cause cancer will be examined. Many of these mechanisms are innovative and differ from the etiological mechanisms of organic carcinogens. These biomedical studies will be complemented by non-biomedical research in sediments and fishes examining the same metals. These studies will help elucidate what factors influence the release of toxic metals and their uptake by humans and wildlife. This application includes 2 biomedical and 2 non-biomedical research projects, 1 Research Support Core, as well as an Administrative Core, Research Translation Core, Training Core, and Community Outreach Core. The biomedical components are: 1.) Epigenetic Mechanisms of Ni, As, Chromate and B[a]P Carcinogenesis (Costa), and 2.) Molecular Mechanisms of Co-carcinogenic effect of As(III) with UV Radiation. The non-biomedical components are: 1.) Genetic and Epigenetic Mechanisms of Toxicities of Mixtures of Aromatic Hydrocarbon and Metal Contaminants to Aquatic Populations, and 2.) Toxicity and Mobilization of PAHs and Cr in Soils and Sediments. All the major pathways that lead to cancer, including genetic damage, epigenetic modifications, and altered signaling pathways are being studied by the biomedical components. Collaboration among biomedical components is catalyzed by the research support core. There is also extensive collaboration between the ecology and engineering components and between the biomedical and non-biomedical, which is enhanced by the Administrative Core and meetings of both the Internal and External Advisory Committees. ADMINISTRATIVE CORE (Costa) Description (provided by applicant) This NYU Superfund Basic Research Program (SBRP) includes projects from a variety of disciplines housed in three academic Institutions in two states. Thus, it is very important that the SBRP Administrative Core provide strong leadership and outstanding administrative support in order to ensure cohesiveness of the entire Program. The NYU SBRP Administrative Core therefore is designed to provide the support that ensures a cohesive and united Program that meets the goals of the NYU SBRP. Therefore, the objectives and specific aims of the NYU SBRP Administrative Core are: 1) Management of the SBRP with the assistance of a Business Administrator who communicates in a timely and consistent manner with the members of the Program, as well as with the NIEHS, providing Program highlights, progress reports, financial reports, etc.;2) Provide assistance to the SBRP Projects and Cores by a Program Associate who coordinates all meetings (Internal Advisory, strategic planning sessions and External Advisory Committees), disseminates documents, prepares documents for the Program members, and coordinates the SBRP monthly seminar series;and 3) Promote collaboration between the Research Projects, Research Support Cores and the activities of the Community Outreach Core and Research Translation Core. The Administrative Core represents the hub of coordination of SBRP research and all other activities. The Administrative Core assures that meetings of the NYU SBRP Internal and External Advisory Committees are held in accordance with the time-line goals. The Administrative Core not only supports the coordination of these various meetings, but also supports the communication between the various projects, cores, and Community Outreach components. Another responsibility of the Administrative Core is the scheduling of the SBRP seminar series speakers, assisting speakers with their travel plans, as well as processing other paperwork related to these presentations. The Administrative Core also assists superfund investigators to attend the yearly superfund meetings. The Administrative personnel are responsible for overseeing the compilation of the grant proposal and yearly progress reports to NIEHS as well as fiscal oversight of the budgetary spending within the Superfund Program in the day-to-day and long-term fiscal operations of the Program. Finally, the Administrative Core is the liaison with the NIEHS and other governmental agencies, providing information to them on the research accomplishments of the NYU SBRP.